Cutting edge: Induction of follicular homing precedes effector Th cell development

Transition from naive to Ag-experienced effector/memory CD4(+) T cells is i nitiated during contact with APC in secondary lymphoid tissue. Here, we dem onstrate that the CXCR5 is a marker for recently activated memory CD4(+) T cells. CXCR5 is rapidly induced during contact with Ag-presenting dendritic cells, well before T cell expansion and effector cell development, and is irreversibly lost on terminally differentiated effector cells. Furthermore, immunization of human volunteers with a recall Ag results in rapid accumul ation of Ag-responsive, CXCR5-expressing CD4(+) T cells in peripheral blood . Early acquisition of a new migration program enables T zone CD4(+) T cell s to develop into follicular B helper T cells or, alternatively, into circu lating memory CD4(+) T cells. Together, CXCR5 unequivocally defines pre-eff ector memory CD4(+) T cells generated during ongoing immune responses.